Strains of dogs with lesion-specific hereditary defects in cardiovascular development (patent ductus arteriosus, valvular pulmonic stenosis, discrete subaortic stenosis, and conotruncal septum defects including tetralogy of Fallot and ventricular septal defect) are used to investigate the following questions: 1. What roles do genetic and environmental factors play in the etiology of congenital heart disease? 2. What are the morphogenetic derangements underlying the anatomic malformations observed at birth? 3. What factors determine the incidence and course of postnatal sequelae of congenital heart disease such as left heart failure and pulmonary hypertension? The relative roles of genetic and environmental factors will be assessed through breeding experiments designed to estimate the heritability of liability to abnormal cardiovascular development. The possible synergism of some known and suspected cardiac teratogens with genetic factors predisposing to congenital heart disease will be investigated by administering these agents to pregnant females whose developing embryos can be predicted to have a low but measurable incidence of congenital heart disease. The ontogeny of the four malformations listed will be studied by retrograde embryologic analysis, utilizing serial sectioning and wax plate reconstruction. The pathogenesis of left heart failure and pulmonary hypertension will be investigated by physiologic and anatomic methods aimed at following changes in pulmonary vascular resistance and pulmonary vascular architecture in pups with patent ductus arteriosus during the first few weeks after birth.